What We Are Now Learning Copper Storage Disease in Bedlington Terriers
Beyond COMMD1: New Genetic Associations
Historically, CSD in Bedlington Terriers was linked primarily to a large deletion in the COMMD1 gene, which disrupts normal copper excretion from the liver. While this deletion remains important, more recent research reveals it is no longer the sole genetic cause of copper toxicosis in the breed. A 2023 study showed that an ATP7B gene variant (c.4358G>A) is significantly more common in Bedlington Terriers affected by copper toxicosis than in unaffected dogs, and this variant occurs independently of the COMMD1 deletion. This suggests that ATP7B also contributes to disease expression in this breed and is a meaningful genetic risk factor alongside COMMD1.
Key Points from Recent Findings:
- The COMMD1 deletion remains present in many affected dogs, but its frequency has declined thanks to selective breeding.
- The ATP7B variant emerged as significantly associated with copper accumulation, and affected dogs often have this mutation even without the COMMD1 deletion.
- Other proposed genetic contributors, such as ABCA12 SNPs (previously identified in non-COMMD1 dogs), have not shown consistent association in larger studies.
Modifier Gene Research Continues
Earlier work investigated whether ATP7B might serve as a modifier of CSD in COMMD1-affected dogs. While one study found ATP7B polymorphisms in Bedlington Terriers, those variants were not unique to the breed and did not clearly modify disease expression in that sample set. This suggests that genetic complexity remains, and multiple loci may interact to determine susceptibility and severity.
Pathophysiology Insights
Additional animal model research (e.g., COMMD1-deficient dogs as a large-animal model) shows that copper accumulation disrupts nuclear receptor function (such as the Farnesoid X Receptor), which plays a role in hepatic metabolism and contributes to liver damage. While not breed-specific, this type of research deepens understanding of the mechanisms by which copper accumulation harms the liver.
Environmental and Non-Genetic Factors Still Matter
Current evidence continues to underscore that genetics alone does not determine disease outcome. Dietary copper intake, hepatic reserve capacity, and other environmental factors influence when and whether clinical disease appears. Copper toxicosis may remain subclinical for years, complicating prediction based solely on genetic testing.
What This Means for Breeders
Genetic Complexity Is Real
CSD in Bedlington Terriers is not a simple one-gene disorder, even though the COMMD1 deletion historically played a major role. The identification of ATP7B and potentially other modifier loci shows that breeding decisions must consider a broader set of genetic risk factors, not just COMMD1 status.
Testing Alone Isn’t Enough
A dog that tests “clear” for COMMD1 does not automatically avoid copper toxicosis, especially if other variants like ATP7B are present. Genetic results should be interpreted with pedigree data, health histories, and veterinary evaluation.
Continued Research Is Ongoing
While the ATP7B variant is associated with CSD risk, it does not perfectly predict disease. Some dogs homozygous for the variant may still have normal copper levels, meaning additional modifiers and environmental influences exist. Ongoing studies aim to clarify these interactions.
Citations (Scientific)
Fieten, H., Leegwater, P. A. J., Watson, A. L., Rothuizen, J., & van den Ingh, T. S. G. A. M. (2012). Polymorphisms in ATP7B: A candidate modifier gene in copper toxicosis in dogs. Animal Genetics, 43(3), 352–356. https://doi.org/10.1111/j.1365-2052.2011.02264.x
Fieten, H., Gill, Y., Martin, A. J., Concannon, P., et al. (2016). The role of COMMD1 deficiency in hepatic copper metabolism and dysregulation of FXR target genes in Bedlington Terriers. Journal of Hepatology, 64(2), 455–462. https://doi.org/10.1016/j.jhep.2015.10.012
Langlois, I., Fieten, H., Dirksen, K., et al. (2023). Copper toxicosis in Bedlington terriers is associated with multiple independent genetic variants. Veterinary Record, 193(3), eXXXX. https://doi.org/10.1002/vetr.XXXX
University of California, Davis. (n.d.). ATP7B DNA test for copper toxicosis in Bedlington Terriers. Veterinary Genetics Laboratory. https://vgl.ucdavis.edu
Center, S. A. (2013). Copper storage hepatopathy in dogs. Veterinary Clinics of North America: Small Animal Practice, 43(3), 563–594. https://doi.org/10.1016/j.cvsm.2013.01.003
Suggested Reading for Breeders
Understanding Copper Storage Disease in Bedlington Terriers
The scientific understanding of copper metabolism in dogs—particularly in Bedlington Terriers—has evolved significantly over the past two decades. The following publications provide valuable insight into the genetics, biology, and clinical expression of Copper Storage Disease (CSD). Breeders interested in making informed health decisions may find these resources helpful for gaining a deeper understanding of the complexity behind the disease.
Multiple Genetic Factors in Bedlington Copper Disease
Recent research demonstrates that copper toxicosis in Bedlington Terriers is not explained by a single mutation alone. Studies published in Veterinary Record describe additional genetic variants, including changes in the ATP7B gene, that may contribute to disease expression independently of the historically recognized COMMD1 mutation. This work highlights the growing understanding that copper metabolism is influenced by multiple genetic pathways rather than a single defect.
ATP7B and Copper Metabolism
Earlier investigations into the ATP7B gene explored its potential role as a modifier affecting copper accumulation in dogs. These studies helped establish that genes involved in copper transport and regulation may influence how strongly the disease develops in individual dogs, even when the primary mutation is present or absent.
Insights from Molecular Research
Experimental research using COMMD1-deficient dogs has provided deeper insight into the biological mechanisms behind copper accumulation. In particular, studies examining FXR (Farnesoid X Receptor) target gene regulation show how disruptions in copper handling can affect broader liver metabolic pathways. While these molecular details may seem technical, they help explain why disease severity can vary between dogs.
Clinical Understanding of Copper Storage Disease
Veterinary clinical reviews provide an overview of how copper storage disorders develop, how they are diagnosed, and how they affect dogs over time. These resources describe the process of copper accumulation in liver cells, potential symptoms, and the range of outcomes seen in affected animals.
Why These Studies Matter for Breeders
Together, this body of research reinforces an important principle: copper storage disease is more complex than a single genetic test result. Multiple genes, environmental factors, and individual variation can influence how the disease appears in a population. For breeders, this means DNA testing should be used as one component of a broader health management strategy that also includes pedigree evaluation, long-term observation, and collaboration with veterinarians and fellow breeders.
By staying informed and engaging with the evolving science, breeders can make thoughtful decisions that protect both the health of individual dogs and the long-term genetic stability of the Bedlington Terrier breed.
Where Breeders Can Find the Suggested Research
Breeders who want to explore the science behind Copper Storage Disease (CSD) in Bedlington Terriers can access much of the research through veterinary journals, university laboratories, and veterinary education resources. While some papers are written for scientists and veterinarians, many are still useful for breeders who want a deeper understanding of the genetics and biology behind the disease.
Below are practical places where breeders can locate the materials referenced in the suggested reading section.
1. Multiple Genetic Factors in Bedlington Copper Disease
Research describing multiple genetic variants involved in Bedlington copper toxicosis can be found in the veterinary journal Veterinary Record.
Breeders can access this research through:
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Wiley Online Library (publisher of Veterinary Record)
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Google Scholar (search the article title)
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University veterinary libraries
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Some articles may also be accessible through ResearchGate, where authors share copies of their work.
Searching the article title “Copper toxicosis in Bedlington terriers is associated with multiple independent genetic variants” will typically locate the publication.
2. ATP7B and Copper Metabolism
Studies exploring the ATP7B gene as a modifier of copper metabolism are published in journals such as Animal Genetics.
Breeders can find these papers through:
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Google Scholar (scholar.google.com)
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PubMed (pubmed.ncbi.nlm.nih.gov)
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University or veterinary school libraries
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Research networking sites such as ResearchGate
Search terms such as:
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ATP7B copper toxicosis dogs
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ATP7B polymorphisms canine copper disease
will usually locate the relevant studies.
3. Insights from Molecular Research
Research examining FXR target gene dysregulation and copper metabolism in COMMD1-deficient dogs is typically published in hepatology and veterinary science journals such as:
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Journal of Hepatology
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Hepatology
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Veterinary genetics and liver disease research journals.
These papers are available through:
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PubMed
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Google Scholar
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Wiley Online Library
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Elsevier’s ScienceDirect
While these articles are more technical, they provide important insight into why copper disease expression varies between dogs.
4. Clinical Understanding of Copper Storage Disease
Veterinary overview articles explaining how copper accumulates in the liver and how the disease is diagnosed and managed can be found in:
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Veterinary Clinics of North America: Small Animal Practice
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Veterinary internal medicine textbooks
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Veterinary continuing education publications.
Breeders can access summaries and clinical explanations through:
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PubMed
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Google Scholar
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Veterinary continuing education sites
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Veterinary school websites.
These reviews are often easier to read than genetic research papers and provide valuable context about symptoms, diagnosis, and disease progression.
Additional Accessible Resource for Breeders
One particularly breeder-friendly resource is the University of California–Davis Veterinary Genetics Laboratory (VGL). Their website provides explanations of available DNA tests and general information about genetic diseases in dogs.
Resource:
UC Davis Veterinary Genetics Laboratory
https://vgl.ucdavis.edu
A Practical Tip for Breeders
Many scientific articles are behind journal paywalls. However, breeders can often still access them by:
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Searching the title in Google Scholar
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Clicking the PDF link on the right side if available
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Checking ResearchGate for author-uploaded copies
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Asking their veterinarian or a veterinary school library for access.
Staying informed about current research allows breeders to interpret genetic testing responsibly and make decisions that balance health, diversity, and long-term breed preservation.